There are numerous laboratory systems and medical and pharmaceutical apparatuses in which it is important to ascertain the fill level in test tubes, microplates, or the like. There are also applications which relate to the detection of liquid-liquid phase boundaries. The term phase boundary is used hereafter both for transitions between gaseous and liquid media (gas-liquid phase boundary) and for transitions between various liquid media (liquid-liquid phase boundary).
In particular if the automation of measuring or experimental sequences is a goal, such an ascertainment of the phase boundary is significant. The fill level ascertainment is typically performed by means of a detection of the liquid level, i.e., the location of the phase boundary between air and liquid is ascertained. This procedure is also referred to as “liquid level detection” (LLD).
Liquid level detection is used, for example, in pipetting devices. Since a gas and a liquid have significantly different dielectric constants, the gas-liquid phase boundary can be determined via a capacitance change.
The detection of liquid-liquid phase boundaries plays an important role, e.g., during a liquid-liquid extraction. It is often important to know the exact phase boundary between aqueous and organic phases. Since non-miscible liquids have significantly different dielectric constants, the liquid-liquid phase boundary can be determined via a capacitance change. This can be used for the purpose of pipetting off an intermediate phase, for example.
In recent years, laboratory apparatuses have become more and more precise and complex. The trend is moving in the direction of higher integration, automation, and parallelism. This results in a high spatial compaction of the individual components and a shortening of the measurement sequences with respect to time. This compaction not only causes mechanical and other design problems, but rather also the precision of the electronic analyzing capability, the mutual influence of adjacent measuring channels, and other aspects may result in problems.
The detection of a phase boundary is typically performed capacitively, as is schematically shown on the basis of FIG. 1. FIG. 1 shows the construction of a known laboratory apparatus 100, which is designed here for detecting a liquid level. The presence of a liquid 1 or the phase boundary between air and liquid 1 is detected here, e.g., by the observation of a capacitance change in Ctlp/liq and in the serial capacitance Ccoupl. An electronic charging/discharging circuit 2 ensures charging and discharging, to be able to measure the effective capacitance between a probe, e.g., in the form of a pipette tip 3, and a grounded base plate 4. The signal processing can be performed using a signal processing circuit 7, which is assisted, e.g., by a controller 8.
The effective capacitance, which results depending on the laboratory apparatus 100 from the stray capacitances, electrical couplings through the probe or the pipette tip 3, the conductivity of the liquid 1, and the crosstalk between adjacent measuring channels (referred to as next tip in FIG. 1) is very small. It is typically in the range of a few Picofarad (pF). The capacitance change, which results upon plunging from the air into a liquid is once again less by approximately a factor of 100 to 1000.
For the detection of phase boundaries, according to an older, but previously unpublished International Patent Application PCT/2010/070599, which was filed on 22 Dec. 2010 claiming the priority of Swiss Patent Application CH 02011/09 of 30 Dec. 2009, a multichannel, capacitively operating measuring device 110 is used. This measuring device 110 comprises, as shown in FIG. 2, one probe 3 (e.g., in the form of a conductive pipette tip or needle) per channel, which is fed into a liquid container 5 of the corresponding channel. During the infeed, a first signal s1(t) having short pulse width and a second signal s2(t) having greater pulse width are processed by a measuring circuit 8, to detect a phase boundary between two media in the liquid container 5 of the corresponding channel.
The device 110 is especially designed for detecting a liquid level (i.e., a gas-liquid phase boundary) in a liquid container 5. However, this device 110 may also be used for ascertaining other phase boundaries. For the purpose of detection, it comprises one probe 3 per channel, which can be fed in the direction of the liquid 1 into the liquid container 5. A circuit 13 having the circuit blocks 2, 7 and a measuring circuit 8, preferably in the form of a controller module, is used, which processes an output signal s(t) of the probe 3, in order to detect a capacitance change upon reaching or piercing the phase boundary. The circuit 13 comprises at least one first filter, in order to filter a first signal s1(t) having short pulse width out of the output signal s(t). In addition, the circuit 13 comprises a second filter, in order to filter a second signal s2(t) having greater pulse width out of the output signal s(t). The measuring circuit 8 has a comparator module, which is designed so that it can be ascertained whether the first signal s1(t) reaches a first threshold value T1. The first threshold value T1 is predefined by the device 110 or the laboratory apparatus 100. In addition to the first threshold value T1, the pulse width P1 can also be ascertained and/or analyzed. In addition, the measuring circuit 8 has a processing module, which is designed so that it can be ascertained whether the second signal s2(t) fulfills at least one predefined second signal criterion (e.g., a minimum slope ST, or a threshold value T2, or a pulse width P2).
FIG. 3 shows a schematic amplitude-time graph, in which two signals s1(t) and s2(t), according to the technical teaching of International Patent Application PCT/2010/070599, of a normal measurement are shown in simplified form. The fundamental mode of operation of the device 110 will be described on the basis of this exemplary illustration. By splitting the signal s(t) by means of two filters into a first signal s1(t) and a second signal s2(t), a very precise statement is made possible. It is nonetheless possible to react immediately based on the first signal s1(t). Such an immediate reaction can be necessary, for example, after the detection of a signal s(t), which appears to be an immersion signal, to cause a stop of the infeed movement B, in order not to immerse more than necessary.
In FIG. 3, a first threshold value T1 is positioned at a relatively small amplitude A. In the simplest embodiment of the device 110, it is only ascertained whether the first signal s1(t) reaches this first threshold value T1. If this is the case, the first criterion for a detection is considered to be fulfilled here.
In FIG. 3, a second threshold value T2 is positioned at an amplitude A, which is above the first threshold value T1. It is now ascertained whether the second signal s2(t) fulfills at least one predefined second signal criterion. In the simplest embodiment of the device 110, it is only ascertained whether the second signal s2(t) reaches this second threshold value T2. If this is the case, the second criterion for a detection is considered to be fulfilled here.
If the first signal criteria and the second signal criteria are fulfilled, as described, the output of an identification (e.g., in the form of a signal or a code) can be performed, for example. This identification indicates that the device 110 has performed a detection of a liquid level.
The higher the degree of integration of such capacitively operating measuring devices, the more problematic it is to be able to recognize the capacitance changes to be measured because of stray capacitances, crosstalk between adjacent channels, and capacitance changes because of moving electrical supply lines.
After the final assembly of a laboratory apparatus, extensive quasi-real test runs for liquid level detection were heretofore performed. For this purpose, the worktable is equipped with mounts (so-called carriers), and with tubes, troughs, and microplates (so-called labware). The equipment of the worktable must be exactly simulated in the test software of the laboratory apparatus. The tubes and the depressions of the microplates (so-called wells) are filled with various volumes of water and water of differing conductivity (deionized water up to physiological table salt solution). In these test runs, the probes of the individual channels are guided successively or in combination with one another (all even/odd channels together, individually or all together) into the corresponding filled test tubes or wells and the signals are analyzed during this procedure. The sensitivity, the wiring, and the crosstalk are tested. A new set of pipette tips must be provided in each case for the individual tests or, if pipetting needles are used, the needles must be washed each time.
In the case of repair or service at the customer, a slightly reduced test program for liquid level detection is applied. Nonetheless, it has been heretofore unavoidable to change the customer-specific equipment of the worktable with carriers, to put on the test-specific carriers, and to reproduce the exact customer equipment after the test.
It is a disadvantage of this approach that the time and work expenditure is relatively large. It is important to fill the correct labware with the correct volume (=fill level) of the liquid having the correct conductivity. It is considered to be a further disadvantage that special worktable equipments having carriers and labware must be used.
With the increasing degree of automation of the laboratory apparatuses, it is additionally desirable to design the corresponding sequences so that it requires no or only little manual intervention. It is to be considered that, e.g., in automated pipetting systems or devices, numerous situations can occur, which cannot be resolved automatically by previous automated pipetting systems or apparatuses.